This research program focuses on the molecular genetics of the parasitic protozoan Leishmania, with particular emphasis on functionally interesting membrane proteins whose expression is regulated during the life cycle of the parasite. In this proposal, several genes for glucose transporter-like proteins that are expressed in a developmentally regulated or stage-specific manner, are studied. An attempt is made to define the biochemical specificity of each transporter by either over- expressing the gene or by targeted gene disruption and studying the subcellular location of each transporter and of several isoforms to determine whether each is targeted to a different membrane domain. A study is also being made of the transcription of one of these genes and attempting to define its promoter, an entity which has not been previously identified for any Leishmania gene. In a new project separate from this proposal, a investigation of a family receptor-adenylate cyclases and their possible roles in signal transduction and in the developmental transformations which occur during the Leishmania life cycle. A long term objective for both of these projects is to understand how the parasite adapts to and survives in the very different environments of its insect vector and its mammalian host. These questions are of fundamental importance to understanding both disease transmission and host colonization for this important pathogen.